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Biology > Drug development and CNS 1 > Flashcards

Drug development and CNS 1 Flashcards

1
Q

What was found wrong with Elixir Sulphanilamide in 1937

A

Found to be contaminated by diethylene glycol, killing 107 people

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2
Q

What was found wrong with Sulfathiazole in 1941

A

Cross contamination with phenobarbital causing 300 deaths

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3
Q

What was the thalidomide controvsy in 1960

A
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4
Q

What was the thalidomide controversy in 1960

A

Was a sleeping tablet, caused 10,000-20,000 birth defects

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5
Q

What’s the first stage of a clinical trial

A

Basic research target selection and pre-clinical research

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6
Q

How long does the first stage of a clinical trial take

A

3- 6 years

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7
Q

What is the second stage of a clinical trial

A

Clinical research phase 1 (healthy individuals)
Clinical research phase (patients for the first time)
Phase 3

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8
Q

How long does the second stage take

A

6-7 years

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9
Q

What’s the last stage of a clinical trial and how long does it take

A

Regulatory review (0.5 - 2 years)

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10
Q

How long and how much money can you spend on a clinical trial

A

15 years and 1 billion

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11
Q

What are the lead findings in drug trials

A

Exploring toxicology, safety

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12
Q

How do you create a controlled environment in preclinical development

A

Providing a safety margin, defining the dose, defining a maximum dose, obtaining regulatory approval of clinical

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13
Q

What does LD50 mean and when was this carried out

A

Increase the dose until 50% died, in 1920

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14
Q

Now what rule is implemented

A

3R - reduce, refine, replace

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15
Q

What is the default non rodent

A

Beagle

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16
Q

What are the three dose groups

A

Low (no toxicity), intermediate, high

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17
Q

What are the general toxicology’s

A

Clinical pathology, haematology, kidney and liver function, coagulation

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18
Q

What are the goals for non-clinical safety evaluations

A

On/ off targets, reversibility, max nontoxic dose and min affective dose, identification of specific monitoring requirements

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19
Q

Examples of withdrawn drugs

A

Sibutramine (appetite suppressant)
Propoxyphene
Drotecogin
Rimonabant
Hydromorphone

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20
Q

Characteristics of a small molecule drug

A

Low molecular weight, chemically synthesised, well-defined structure

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21
Q

Characteristics of a biological molecule and monoclonal antibodies

A

High molecular weight, derived from living organisms, large and complex structure

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22
Q

How much have biologics accounted for in new medicine approvals

A

one third

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23
Q

Examples of vaccines

A

HPV, COVID-19

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24
Q

What are RNAi

A

interfering RNA molecules

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25
Q

What are cell based therapies

A

Taking a whole cell out of a patient, modify then grow. Then inject back into patient

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26
Q

Example for when cell based therapies are useful

A

Children with acute lymphoblastic leukemi

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27
Q

Example of when cell based therapies are useful

A

Children with acute lymphoblastic leukaemia

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28
Q

What is the phase 1 dose

A

Minimum anticipated biological effect

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29
Q

What is immunotherapy

A

A form of cancer treatment, uses immune system to attack cancer cells

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30
Q

What do checkpoint inhbitors do

A

Release natural brake on your immune system so that immune cells called t cells recognise and attack tumors

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31
Q

What do checkpoint inhbitors do

A

Release natural brake on your immune system so that immune cells called t cells recognise and attack tumours

32
Q

What is CAR T cell therapy

A

Scientists engineer a patient’s own immune cells to make a new protein

33
Q

Who discovered nitrous oxide and when

A

Horace Wells in the mid 1800s

34
Q

How are general anaesthetics characterised

A

By how the chemicals are administered to induce a state of anaesthesia

35
Q

What are chemical inhalational anaesthetics and example

A

Nitrous oxide and through the lungs

36
Q

What are intravenous anaesthetics and example

A

Administered directly into the circulation system and steroids, barbitruates and halogenated hydrocarbions

37
Q

Whay are ethers and chloroform not used anymore

A

They can vapourise at low temperatures and are highly explosive and flammable

38
Q

What are physical anesthetics

A

Low pressure (atmospheric) and cold temperatures such as hypothermia

39
Q

What is the lipid theory of general anaesthetics

A

The idea that somehow these drugs cause membrane expansion

40
Q

What is the Meyer- overton rule

A

The anaesthetic effect was considered proportional to the molar concentratiof the agent in lipid

41
Q

What are the problems with the lipid theory of general anaesthetics

A

There’s no temperature effect, no binding sites, no loss of activity with homologoys series of lipophilic compounds and no increase in GABA A

42
Q

What do low concentrations of volatile gases activate

A

Two pore domain K channels

43
Q

What does ketamine and nitrous oxide block

A

NDMS receptors

44
Q

What does an increase in inhibitory neurotransmission through GABA A receptors lead to

A

Inhibition in neural networks

45
Q

What does an increase in inhibitory neurotranmission of reticular formation lead to

A

Unconciousness

46
Q

What does an increase in inhibitory neurotransmission through the hippocampus lead to

A

Short term memory loss/ amnesia

47
Q

What happens as the concetration of anesthetics is increased

A

Inhibition in the CNS, leading to loss of motor control, absejce of artificial respiration leading to death

48
Q

4 stages of anaesthesia

A
  1. Analgesia
  2. Excitement state
  3. Surgical aneasthesia
  4. Medullary paralysis
49
Q

What are the ideal conditons from anaestheia

A

Rapid induction and loss of conciousnes, good analgesia, muscle relaxation, rapid recovy

50
Q

Advantages of intravenous anaesthetics

A

Easy to administer, rapid induction, short duration of action

51
Q

Disdvantages of intravenous anaesthetics

A

Pain at the site of infection, complex pharmacokinetics

52
Q

Disadvantages of thiopental and what is it an example of

A

A barbituate intravenous drug. It has a high lipid soluability, low therapeutic index

53
Q

Side effects of intravenous drugs

A

Respitary depression, cardiovascular deprssion

54
Q

What is ketamine

A

A dissociative anaesthetic

55
Q

What does ketamine do

A

Causes sensory loss, powerful analgesic, causes amnesia

56
Q

What are the side effects of ketamine

A

Increased CV excitement, involuntary movements, increased intracranial pressure, hallucinations, delirium, irrational behaviour

57
Q

What is ketamine used for

A

In pediatrics (with BZD) and vetinary, starting to be used for depression in adults

58
Q

Examples of inhalational anaesthetics

A

Isoflurane, desflurane and sevoflurane

58
Q

Examples of inhalational anaesthetics

A

Isoflurane, desflurane and sevoflurane

59
Q

What are anxiolytics

A

Drugs used to treat anxiety

60
Q

What are hypnotics

A

Drugs used to treat sleep disorders

61
Q

What hormone is secreted when fear response is activated

A

Cortisol

62
Q

What is a fear response characterised by

A

Defensive behaviours, autonomic reflexes, alertness, corticosteroid secretion and negative emotions

63
Q

Examples of anxiety disorders

A

Panic disorder, phobias, social anxiety, PTSD, OCD, generalised anxiety

64
Q

Treatments for anxiety

A

Benzodiazepines and barbiturates, antidepressants, antiepileptics and antipsychotics

65
Q

Examples of animal models of anxiety

A

Elevated cross test, the light/ dark box

66
Q

What are GABA A receptors targets for

A

Anxioltyics and hypnotics

67
Q

What is a GABA A receptor

A

A lingand gated ion channel

68
Q

What is a GABA B receptor

A

A g coupled receptor

69
Q

What is picrotoxin

A

A non competitive agonist of the GABA receptor by blocking the pore

70
Q

What is the second site at the GABA receptor known as

A

The positive allosteric regulator

71
Q

What does the allosteric modulator do

A

Doesn’t activate receptor on its own, it modifies the behaviour of the receptor when agonist is bound to the orthostatic site

72
Q

What are the physiological effects of the benzodiapene agonists

A

Sedation, hypnosis, anterograde amnesia, anti- convulsant, reduction of muscle tone

73
Q

What are the adverse effects of benzodiapene agonists

A

Decreased tolerance due to increased exposure, misuse, physical dependance,

74
Q

What is epivario useful for

A

Post traumatic stress disorder- prevents the consolidation of the memory

Biology (9 decks)

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